Effects of an oral treatment with concentrated grape juice (ENT) on cell NOS (eNOS and iNOS) expression and proliferation in experimentally induced carcinoma in mice

Abstract

The exact role of nitric oxide (NO) in tumour development has not been yet fully elucidated. The concentrated grape juice (ENT) is particularly rich in polyphenols and is actually considered as an additive food with antioxidant properties. The present study investigates the eventual effects of ENT on cell proliferation and NO production within mammary carcinomas experimentally induced by a subcutaneous injection of 2.10(6) EAC (Ehrlich Ascite Carcinoma) cells in mice. For that, 28 female balb/c mice were randomly divided into 2 equal groups: mice were daily orally treated with ENT (0.5 mL/day) (ENT group) or with 0.9% NaCl (0.5 mL/day) for 7 consecutive days before carcinoma induction and 22 days after. On day 30, animals were slaughtered under ether anaesthesia and PCNA, eNOS and iNOs expressions in turnout tissues were evaluated by immunohistochemistry: proliferation indexes (percentages of PCNA positive cells in 1 000 cells) and the respective eNOS and iNOS HSCORE values (cumulated percentages of positive stained cells according to the staining intensity X staining intensity) were then calculated. The ENT treatment has significantly reduced the proliferation indexes of the tumours. Moreover, tumour iNOS expression was dramatically lowered compared to controls whereas the eNOS expression was weakly affected. These results suggest that carcinoma growth was restricted in mice orally treated with ENT because of the marked reduction of iNOS expression.